NNC0194-0499 and Semaglutide combination investigated for reducing liver damage in NASH

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by inflammation and liver cell damage, often leading to fibrosis, cirrhosis, and liver failure. Current treatment options are limited, with lifestyle modifications being the primary recommendation. Semaglutide, a well-known GLP-1 receptor agonist, has shown promise in improving liver damage and promoting weight loss. NNC0194-0499 is a novel investigational medicine designed to act directly in the liver, potentially offering a complementary mechanism to semaglutide. This study explores whether combining these agents, or semaglutide with another weight-loss medicine, NNC0174-0833 (cagrilintide), could offer superior efficacy in reducing liver damage in NASH compared to monotherapy or placebo.

This randomized, placebo-controlled clinical trial investigated the efficacy of combination therapies in NASH patients. Participants received weekly subcutaneous injections over approximately 19 months. Treatment arms included NNC0194-0499 and semaglutide in combination, semaglutide and NNC0174-0833 (cagrilintide) in combination, or one active medicine plus placebo, or dual placebo. Treatment assignment was randomized. The primary endpoint was reduction in liver damage, assessed via 1 or 2 liver biopsies (at baseline and study end). Participants underwent 14 clinic visits and 9 phone calls for monitoring.